Elsevier

Endocrine Practice

Volume 19, Issue 2, March–April 2013, Pages 252-258
Endocrine Practice

Original Articles
Persistence of Cushing’S Disease
Persistence of Cushing’s Disease Symptoms and Comorbidities After Surgical Cure: a Long-Term, Integral Evaluation

https://doi.org/10.4158/EP12247.ORGet rights and content

ABSTRACT

Objective

Successful surgery does not always resolve all the clinical consequences of hypercortisolism in patients with Cushing’s disease (CD). Our purpose was to integrally evaluate a group of CD patients cured by pituitary surgery and look for the persistence of CD symptoms, signs, and comorbidities.

Methods

We performed clinical and biochemical evaluations of 29 CD patients (2 males) cured by pituitary surgery. All patients underwent early (median 12 months) and late (median 58 months) postoperative evaluations. We sought information regarding hypercortisolism-related symptoms and signs, as well as metabolic, cardiovascular, reproductive, and psychologic comorbidities.

Results

The prevalence of obesity dropped from 72.4% at diagnosis to 31% at early evaluation but increased again to 44.8% at the late evaluation. Diabetes was present in 14 patients (48.3%) at diagnosis and persisted in 9 at the late evaluation. Hypertriglyceridemia was present in 58.6% and 55.1% of patients at diagnosis and at the late follow-up, respectively. The prevalence of hypercholesterolemia was 79.3% at diagnosis, decreased to 55.1% at the early evaluation, and increased to 65.5% at the late evaluation. Menstrual abnormalities were originally present in 15 of 20 women, and 8 of the 15 had recovered normal periods when seen at the last evaluation. Among the 24 patients with depression at diagnosis, 11 and 6 still exhibited mood abnormalities at the early and late evaluations, respectively.

Conclusion

In a variable proportion of patients, the cardiovascular, metabolic, and emotional comorbidities of CD persist after long-term remission, irrespective of the initial degree of hypercortisolism. (Endocr Pract. 2013; 19:252-258)

Section snippets

INTRODUCTION

The complications and comorbidities of Cushing’s disease (CD) were thought for the most part to be reversible upon normalization of hypercortisolism by successful removal of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma (1). However, recent longterm follow-up of surgically cured patients has suggested that some of the consequences of the previous glucocorticoid excess do not remit completely upon normalization of the corticotrophic axis. Persistent clinical abnormalities

METHODS

The study included patients who had undergone surgery for pituitary ACTH-producing adenomas at the Hospital de Especialidades, Centro Médico Nacional S. XXI, IMSS between July 1997 and March 2010. Our inclusion criteria were as follows: (1) documentation of CD either by bilateral inferior petrosal sinus sampling or positive ACTH immunostaining of the excised adenoma tissue; (2) complete preoperative clinical and biochemical information; (3) documentation of postoperative biochemical cure one to

Statistical Analysis

Quantitative data are presented as means ± standard deviation (SD) when normally distributed and as medians with interquartile ranges (IQRs) when not. Data distributions were ascertained with Shapiro-Wilk tests. The proportions of each clinical variable were reported before and after surgical treatment. McNemar’s test for dependent samples was performed to assess differences among proportions at diagnosis and at both postsurgical evaluations. To ascertain if symptom and comorbidity persistence

RESULTS

The study included 29 patients (27 women; mean age at diagnosis of 35.6 ± 8.4 years; range, 16 to 57 years) who met the biochemical CD cure criteria after pituitary surgery. Table 1 depicts the basal characteristics of the patients prior to pituitary surgery. Twenty-four patients (82.7%) developed acute hypocortisolism (mean serum cortisol, 1 ± 0.7 μg/dL) within 15 days of surgery and were maintained on glucocorticoid replacement therapy (prednisone 5 mg daily, oral hydrocortisone is not

DISCUSSION

This is the first investigation that systematically assessed the persistence of CD comorbidites at 2 different time points after resolution of hypercortisolism by TSS. Previous studies have chosen to evaluate specific elements of metabolic syndrome, including body fat distribution and obesity (6), glucose metabolism abnormalities and diabetes (2., 3., 4., 5.), dyslipidemia (2., 3., 4., 5., 6.), and hypertension (3,8). The majority of these have compared cured CD patients to either biochemically

CONCLUSION

We conclude that in a variable proportion of patients, some of the metabolic and emotional comorbidities of CD persist after long-term surgical remission, irrespective of the initial degree of hypercortisolism. We postulate that such persistence is in some way related to the recently reported increased mortality in these patients, even after their condition is successfully cured (17., 18.).

DISCLOSURE

The authors have no multiplicity of interest to disclose.

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